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Multiscale modeling of genome organization with maximum entropy optimization
Three-dimensional (3D) organization of the human genome plays an essential role in all DNA-templated processes, including gene transcription, gene regulation, and DNA replication. Computational modeling can be an effective way of building high-resolution genome structures and improving our understan...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AIP Publishing LLC
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253599/ https://www.ncbi.nlm.nih.gov/pubmed/34241389 http://dx.doi.org/10.1063/5.0044150 |
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author | Lin, Xingcheng Qi, Yifeng Latham, Andrew P. Zhang, Bin |
author_facet | Lin, Xingcheng Qi, Yifeng Latham, Andrew P. Zhang, Bin |
author_sort | Lin, Xingcheng |
collection | PubMed |
description | Three-dimensional (3D) organization of the human genome plays an essential role in all DNA-templated processes, including gene transcription, gene regulation, and DNA replication. Computational modeling can be an effective way of building high-resolution genome structures and improving our understanding of these molecular processes. However, it faces significant challenges as the human genome consists of over 6 × 10(9) base pairs, a system size that exceeds the capacity of traditional modeling approaches. In this perspective, we review the progress that has been made in modeling the human genome. Coarse-grained models parameterized to reproduce experimental data via the maximum entropy optimization algorithm serve as effective means to study genome organization at various length scales. They have provided insight into the principles of whole-genome organization and enabled de novo predictions of chromosome structures from epigenetic modifications. Applications of these models at a near-atomistic resolution further revealed physicochemical interactions that drive the phase separation of disordered proteins and dictate chromatin stability in situ. We conclude with an outlook on the opportunities and challenges in studying chromosome dynamics. |
format | Online Article Text |
id | pubmed-8253599 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | AIP Publishing LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-82535992021-07-12 Multiscale modeling of genome organization with maximum entropy optimization Lin, Xingcheng Qi, Yifeng Latham, Andrew P. Zhang, Bin J Chem Phys Perspectives Three-dimensional (3D) organization of the human genome plays an essential role in all DNA-templated processes, including gene transcription, gene regulation, and DNA replication. Computational modeling can be an effective way of building high-resolution genome structures and improving our understanding of these molecular processes. However, it faces significant challenges as the human genome consists of over 6 × 10(9) base pairs, a system size that exceeds the capacity of traditional modeling approaches. In this perspective, we review the progress that has been made in modeling the human genome. Coarse-grained models parameterized to reproduce experimental data via the maximum entropy optimization algorithm serve as effective means to study genome organization at various length scales. They have provided insight into the principles of whole-genome organization and enabled de novo predictions of chromosome structures from epigenetic modifications. Applications of these models at a near-atomistic resolution further revealed physicochemical interactions that drive the phase separation of disordered proteins and dictate chromatin stability in situ. We conclude with an outlook on the opportunities and challenges in studying chromosome dynamics. AIP Publishing LLC 2021-07-07 2021-07-01 /pmc/articles/PMC8253599/ /pubmed/34241389 http://dx.doi.org/10.1063/5.0044150 Text en © 2021 Author(s). https://creativecommons.org/licenses/by/4.0/All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ). |
spellingShingle | Perspectives Lin, Xingcheng Qi, Yifeng Latham, Andrew P. Zhang, Bin Multiscale modeling of genome organization with maximum entropy optimization |
title | Multiscale modeling of genome organization with maximum entropy optimization |
title_full | Multiscale modeling of genome organization with maximum entropy optimization |
title_fullStr | Multiscale modeling of genome organization with maximum entropy optimization |
title_full_unstemmed | Multiscale modeling of genome organization with maximum entropy optimization |
title_short | Multiscale modeling of genome organization with maximum entropy optimization |
title_sort | multiscale modeling of genome organization with maximum entropy optimization |
topic | Perspectives |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253599/ https://www.ncbi.nlm.nih.gov/pubmed/34241389 http://dx.doi.org/10.1063/5.0044150 |
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